Psilocybin for Depressive Disorders

164 papers and 41 clinical trials exploring psilocybin as a treatment for depressive disorders.

CompoundClassic Psychedelic

Psilocybin

Psilocybin is a naturally occurring tryptamine psychedelic that acts as a prodrug to psilocin, a potent 5-HT2A receptor agonist. It is the furthest advanced psychedelic in clinical development, with two positive Phase III trials in treatment-resistant depression and expanding regulated access in Australia, Germany, and US states.

Full Psilocybin profile
IndicationApproximately 260 million people worldwide are affected by depression.

Depressive Disorders

Depressive disorders, particularly major depressive disorder (MDD), are significant contributors to global mental health issues. Research into the therapeutic potential of psychedelics, such as psilocybin and ketamine, offers promising avenues for treatment, especially for cases that are resistant to conventional therapies.

Full Depressive Disorders profile

Academic Research

164 papers
Open Accessindividual

Effects of LSD and Psilocybin on Heart Rate in Patients Receiving Psychedelic Treatment for Depressive and Anxiety Disorders: A Retrospective Observational Study

In this retrospective study of 30 patients receiving LSD or psilocybin for treatment‑resistant depression or anxiety, LSD produced a delayed, sustained increase in heart rate peaking at 3–4 hours while psilocybin showed an earlier decline, with a significant time × substance interaction that persisted after adjusting for age and anxiety and no serious cardiovascular events observed. These preliminary findings suggest distinct temporal cardiovascular profiles for LSD versus psilocybin but should be interpreted cautiously given the retrospective design, small sample and dose imbalance.

Published
Journal
Psychology International
Authors
Cheng, M., Aboulafia-Brakha, T., Buchard, A., Boyanova Anastasova, R., Girani, L., Breitenmoser, A., Alaux, S., Mabilais, C., Amberger, C., Seragnoli, F., Furtado, L., Thorens, G., Zullino, D., Penzenstadler, L.
Open Accessindividual

Real-World Psilocybin Therapy for Treatment-Resistant Depression: a Retrospective Observational Study

In a retrospective case series of 19 treatment‑resistant depression patients treated with 20–35 mg psilocybin in routine clinical practice, depressive symptoms decreased significantly with large effect sizes on MADRS and BDI, though response and remission rates were lower than in controlled trials and no additive benefit of multiple doses was found. No serious adverse events occurred, but the observational design and small sample size mean larger prospective studies are needed to confirm effectiveness and identify predictors of response.

Published
Journal
Preprints
Authors
Jungwirth, J., Westenhöfer, S., Aicher, H., Provaznikova, B., Kronenberg, G., Seifritz, E., Prinz, S., Olbrich, S.
Paywallindividual

The Relationship Between Participant Pretreatment Clinical Presentation and the Quality of Psilocybin Experience: A Retrospective Analysis

In a retrospective analysis of 233 participants with treatment‑resistant depression given 1, 10 or 25 mg COMP360 psilocybin, dose was the strongest and most consistent predictor of the acute psychedelic experience, while pretreatment clinical characteristics made only modest, variable contributions (positive affect, lower generalized anxiety, higher executive function and greater personality‑disorder symptoms each influenced different experience dimensions). These results challenge the assumption that pretreatment traits are major determinants of the subjective psilocybin experience.

Published
Journal
Journal of Clinical Psychopharmacology
Authors
Kirlić, N., Atli, M., Mistry, S., Gold, M., Goodwin, G. M.
Open Accessindividual

Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial

This secondary analysis (n=26) of adults with treatment-resistant depression from an open-label psilocybin-assisted psychotherapy trial found statistically significant improvements in processing speed and executive function at two weeks post-treatment, with gains on Trail Making Tests remaining significant after adjusting for depressive symptoms; however, reliable change indices showed that the proportion of participants achieving meaningful improvement (4.2–12.5%) did not exceed chance expectations, suggesting observed gains may reflect practice effects rather than genuine procognitive benefits.

Published
Journal
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Authors
Johnson, D. E., Meshkat, S., Kaczmarek, E. S., Rabin, J. S., Brudner, R. M., Chisamore, N., Doyle, Z., Bawks, J., Riva-Cambrin, J., Mansur, R. B., Lipsitz, O., McIntyre, R. S., Lanctôt, K. L., Rosenblat, J. D.

Clinical Trials

41 trials
Not yet recruitingPhase I

A Phase 1, Open-label, Single-arm Basket Trial of the Intravenously Administered Psilocin (TRP-8803): Safety, Anxiety, and Quality of Life Across Health Conditions Characterised by Cognitive Inflexibility, Emotional Distress, and Persistent Bodily Symptom Burden

This Phase 1, open‑label, single‑arm basket trial (N=66) tests the safety and early clinical effects of intravenous psilocin (TRP‑8803) administered in two dosing sessions alongside psychotherapy over a 6‑week treatment period, with a 12‑week follow‑up. Conducted in Australia and sponsored by Tryp Therapeutics, the study enrols participants across ten diagnostic cohorts — anorexia nervosa, body dysmorphic disorder, chronic fatigue, fibromyalgia, generalised anxiety disorder, irritable bowel syndrome, long COVID, major depressive disorder, obsessive–compulsive disorder and post‑traumatic stress disorder — to evaluate tolerability and signals of benefit in anxiety and quality of life. As a Phase 1 trial the primary outcomes focus on safety and tolerability (adverse events, vital signs and treatment‑emergent effects), with secondary or exploratory outcomes assessing changes in anxiety symptoms and health‑related quality of life using standardised, validated instruments. The single‑arm, open‑label design means there is no placebo or active comparator, and efficacy assessments are intended to generate preliminary, hypothesis‑generating data to inform the design of subsequent controlled studies. The study began recruitment in November 2025.

Started
Type
interventional
Blinding
none
Randomized
Yes
Registry ID
12625000949482

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Search all Psilocybin papers Search all Depressive Disorders trials Full Psilocybin profile Full Depressive Disorders profile